Study protocol: asking questions about alcohol in pregnancy (AQUA): a longitudinal cohort study of fetal effects of low to moderate alcohol exposure

Despite extensive research, a direct correlation between low to moderate prenatal alcohol exposure (PAE) and Fetal Alcohol Spectrum Disorders has been elusive. Conflicting results are attributed to a lack of accurate and detailed data on PAE and incomplete information on contributing factors. The public health effectiveness of policies recommending complete abstinence from alcohol during pregnancy is challenged by the high frequency of unplanned pregnancies, where many women consumed some alcohol prior to pregnancy recognition. There is a need for research evidence emphasizing timing and dosage of PAE and its effects on child development

Development and evaluation of tools and an intervention to improve patient- and carer-centred outcomes in Longer-Term Stroke care and exploration of adjustment post stroke: the LoTS care research programme

Background: Evidence-based care pathways are required to support stroke patients and their carers in the longer term. Aims: The twofold aim of this programme of four interlinking projects was to enhance the care of stroke survivors and their carers in the first year after stroke and gain insights into the process of adjustment. Methods and results: We updated and further refined a purposely developed system of care (project 1) predicated on a patient-centred structured assessment designed to address areas of importance to patients and carers. The structured assessment is linked to evidence-based treatment algorithms, which we updated using a structured protocol: reviewing available guidelines, Cochrane reviews and randomised trials. A pragmatic cluster randomised controlled trial evaluation of the clinical effectiveness and cost-effectiveness of this system of care was undertaken in 29 community-based UK stroke care co-ordinator services (project 2). In total, 15 services provided the system of care and 14 continued with usual practice. The primary objective was to determine whether the intervention improved patient psychological outcomes (General Health Questionnaire-12) at 6 months; secondary objectives included functional outcomes for patients, outcomes for carers and cost-effectiveness, as measured through self-completed postal questionnaires at 6 and 12 months. A total of 800 patients and 208 carers were recruited; numbers of participants and their baseline characteristics were well balanced between intervention and control services. There was no evidence of statistically significant differences in primary or secondary end points or adverse events between the two groups, nor evidence of cost-effectiveness. Intervention compliance was high, indicating that this is an appropriate approach to implement evidence into clinical practice. A 22-item Longer-term Unmet Needs after Stroke (LUNS) questionnaire was developed and robustly tested (project 3). A pack including the LUNS questionnaire and outcome assessments of mood and social activity was posted to participants 3 or 6 months after stroke to assess acceptability and validity. The LUNS questionnaire was re-sent 1 week after return of the first pack to assess test–retest reliability. In total, 850 patients were recruited and the acceptability, validity and test–retest reliability of the LUNS questionnaire as a screening tool for post-stroke unmet need were confirmed. This tool is now available for clinical use. An in-depth qualitative investigation was undertaken with 22 patients (and carers) at least 1 year after stroke (project 4) to gain further insights into the experience of adjustment. This included initial semistructured interviews, limited observations and solicited diaries with a follow-up interview 3–4 months after the initial interview and highlighted a range of different trajectories for post-stroke recovery. Conclusions: The programme has been completed as planned, including one of the largest ever stroke rehabilitation trials. This work highlights that successfully addressing the needs of a heterogeneous post-stroke population remains problematic. Future work could explore stratifying patients and targeting services towards patients (and carers) with specific needs, leading to a more specialised bespoke service. The newly developed LUNS questionnaire and the qualitative work will help inform such services

Automatic phonological activation during visual word recognition in bilingual children:a cross-language masked priming study in Grades 3 and 5

International audienc

Reduced dietary salt for the prevention of cardiovascular disease.

BACKGROUND: An earlier Cochrane review of dietary advice identified insufficient evidence to assess effects of reduced salt intake on mortality or cardiovascular events. OBJECTIVES: 1. To assess the long term effects of interventions aimed at reducing dietary salt on mortality and cardiovascular morbidity.2. To investigate whether blood pressure reduction is an explanatory factor in any effect of such dietary interventions on mortality and cardiovascular outcomes. SEARCH STRATEGY: The Cochrane Library (CENTRAL, Health Technology Assessment (HTA) and Database of Abstracts of Reviews of Effect (DARE)), MEDLINE, EMBASE, CINAHL and PsycInfo were searched through to October 2008. References of included studies and reviews were also checked. No language restrictions were applied. SELECTION CRITERIA: Trials fulfilled the following criteria: (1) randomised with follow up of at least six-months, (2) intervention was reduced dietary salt (restricted salt dietary intervention or advice to reduce salt intake), (3) adults, (4) mortality or cardiovascular morbidity data was available. Two reviewers independently assessed whether studies met these criteria. DATA COLLECTION AND ANALYSIS: Data extraction and study validity were compiled by a single reviewer, and checked by a second. Authors were contacted where possible to obtain missing information. Events were extracted and relative risks (RRs) and 95% CIs calculated. MAIN RESULTS: Seven studies (including 6,489 participants) met the inclusion criteria - three in normotensives (n=3518), two in hypertensives (n=758), one in a mixed population of normo- and hypertensives (n=1981) and one in heart failure (n=232) with end of trial follow-up of seven to 36 months and longest observational follow up (after trial end) to 12.7 yrs. Relative risks for all cause mortality in normotensives (end of trial RR 0.67, 95% CI: 0.40 to 1.12, 60 deaths; longest follow up RR 0.90, 95% CI: 0.58 to 1.40, 79 deaths) and hypertensives (end of trial RR 0.97, 95% CI: 0.83 to 1.13, 513 deaths; longest follow up RR 0.96, 95% CI; 0.83 to 1.11, 565 deaths) showed no strong evidence of any effect of salt reduction. Cardiovascular morbidity in people with normal blood pressure (longest follow-up RR 0.71, 95% CI: 0.42 to 1.20, 200 events) or raised blood pressure at baseline (end of trial RR 0.84, 95% CI: 0.57 to 1.23, 93 events) also showed no strong evidence of benefit. Salt restriction increased the risk of all-cause death in those with congestive heart failure (end of trial relative risk: 2.59, 95% 1.04 to 6.44, 21 deaths). We found no information on participants health-related quality of life. AUTHORS' CONCLUSIONS: Despite collating more event data than previous systematic reviews of randomised controlled trials (665 deaths in some 6,250 participants), there is still insufficient power to exclude clinically important effects of reduced dietary salt on mortality or cardiovascular morbidity in normotensive or hypertensive populations. Further RCT evidence is needed to confirm whether restriction of sodium is harmful for people with heart failure. Our estimates of benefits from dietary salt restriction are consistent with the predicted small effects on clinical events attributable to the small blood pressure reduction achieved

Familial hypercholesterolaemia: identification and management. Evidence reviews for case-finding, diagnosis and statin monotherapy

This guideline covers identifying and managing familial hypercholesterolaemia (FH), a specific type of high cholesterol that runs in the family, in children, young people and adults. It aims to help identify people at increased risk of coronary heart disease as a result of having FH. In November 2017, we reviewed the evidence for case finding and diagnosis, identification using cascade testing, and management using statins. We amended recommendations in sections 1.1, 1.2 and 1.3

Particles and fields in fluid turbulence

The understanding of fluid turbulence has considerably progressed in recent years. The application of the methods of statistical mechanics to the description of the motion of fluid particles, i.e. to the Lagrangian dynamics, has led to a new quantitative theory of intermittency in turbulent transport. The first analytical description of anomalous scaling laws in turbulence has been obtained. The underlying physical mechanism reveals the role of statistical integrals of motion in non-equilibrium systems. For turbulent transport, the statistical conservation laws are hidden in the evolution of groups of fluid particles and arise from the competition between the expansion of a group and the change of its geometry. By breaking the scale-invariance symmetry, the statistically conserved quantities lead to the observed anomalous scaling of transported fields. Lagrangian methods also shed new light on some practical issues, such as mixing and turbulent magnetic dynamo.Comment: 165 pages, review article for Rev. Mod. Phy

Thermodynamics of the Reduction Roasting of Nickeliferous Laterite Ores

Abstract The global nickel sulphide resources are becoming more difficult to mine and, as a result, there is increasing interest in the current and future development of the oxidic nickel laterite deposits. In comparison to the sulphide ores, the nickel laterites cannot be readily upgraded by conventional means and growing attention is being focused on the development of new methods for processing these ores. In this paper, firstly, brief overviews of laterite ore mineralogy and the conventional techniques used to extract the nickel from both the limonitic and the saprolitic nickeliferous laterites are provided. Secondly, previous research on the thermodynamic modelling of the reduction of the laterites is discussed. Thirdly, an improved thermodynamic model is used to predict the equilibrium products arising from the solid state reduction of both the limonitic and the saprolitic ores. Based on these thermodynamic predictions, the reduction behaviors of the two ore types are compared in terms of nickel recovery and grade in the ferronickel product. The effects of reduction temperature, ore composition and carbon additions were studied. Finally, the results from the simulations are compared to the experimental data available in the literature

The realtionship between common patterns of prenatal alcohol exposure and the neurodevelopment of two-year old children

Background: Around 60% of women drink some alcohol while pregnant. There is conflicting evidence on the effect on the fetus of common patterns of prenatal alcohol exposure (PAE) e.g. low level or sporadic drinking. Guidelines recommend abstinence as the safest option, creating problems for those advising women who drink at these levels before pregnancy recognition or beyond. The Asking QUestions about Alcohol (AQUA) study aimed to accurately measure PAE and account for important cofactors, to reduce uncertainty about child outcomes. Method: Detailed data on PAE were prospectively collected in a pre-birth cohort of over 1500 mother/child dyads. There was also extensive data collection of predictors of child development at one and two-year's post-partum. A sub-group of children was followed up at two years of age with a neurodevelopmental assessment (Bayley III). Two-step multivariable regression analyses of an effect of PAE accounted for independent risk factors that related to 1) pregnancy, including sociodemographic, psychologic and lifestyle variables such as diet and supplement use, and 2) the postnatal care-giving environment, including breastfeeding and maternal psychological wellbeing. Results: Adjustment for independent risk factors ameliorated any putative associations between PAE and cognitive, language and motor development in 554 two year-old children spread evenly across six PAE groups. Conclusions: Assessing neurodevelopmental outcomes associated with PAE is strongly influenced by other modifiable and non-modifiable risk factors. Although we found no adverse neurodevelopmental outcomes at two years of age, follow-up will be necessary in these children when complex higher-level cognitive, language and motor skills are required

A data driven approach to identify trajectories of prenatal alcohol consumption in an Australian population-based cohort of pregnant women.

Accurate information on dose, frequency and timing of maternal alcohol consumption is critically important when investigating fetal risks from prenatal alcohol exposure. Identification of distinct alcohol use behaviours can also assist in developing directed public health messages about possible adverse child outcomes, including Fetal Alcohol Spectrum Disorder. We aimed to determine group-based trajectories of time-specific, unit-level, alcohol consumption using data from 1458 pregnant women in the Asking Questions about Alcohol in Pregnancy (AQUA) longitudinal study in Melbourne, Australia. Six alcohol consumption trajectories were identified incorporating four timepoints across gestation. Labels were assigned based on consumption in trimester one and whether alcohol use was continued throughout pregnancy: abstained (33.8%); low discontinued (trimester one) (14.4%); moderate discontinued (11.7%); low sustained (13.0%); moderate sustained (23.5%); and high sustained (3.6%). Median weekly consumption in trimester one ranged from 3 g (low discontinued) to 184 g of absolute alcohol (high sustained). Alcohol use after pregnancy recognition decreased dramatically for all sustained drinking trajectories, indicating some awareness of risk to the unborn child. Further, specific maternal characteristics were associated with different trajectories, which may inform targeted health promotion aimed at reducing alcohol use in pregnancy

Neutrophils in animal models of autoimmune disease

Neutrophils have traditionally been thought to play only a peripheral role in the genesis of many autoimmune and inflammatory diseases. However, recent studies in a variety of animal models suggest that these cells are central to the initiation and propagation of autoimmunity. The use of mouse models, which allow either deletion of neutrophils or the targeting of specific neutrophil functions, has revealed the many complex ways these cells contribute to autoimmune/inflammatory processes. This includes generation of self antigens through the process of NETosis, regulation of T-cell and dendritic cell activation, production of cytokines such as BAFF that stimulate self-reactive B-cells, as well as indirect effects on epithelial cell stability. In comparing the many different autoimmune models in which neutrophils have been examined, a number of common underlying themes emerge - such as a role for neutrophils in stimulating vascular permeability in arthritis, encephalitis and colitis. The use of animal models has also stimulated the development of new therapeutics that target neutrophil functions, such as NETosis, that may prove beneficial in human disease. This review will summarize neutrophil contributions in a number of murine autoimmune/inflammatory disease models. © 2016 Elsevier Ltd